The Host Defense Group of the Laboratory of Respiratory Biology, Division of Intramural Research, National Institute of Environmental Health Sciences, headed by Michael B. Fessler, MD now enters its fourth year at the NIEHS since inception. We have now published several reports: 1. an original publication that defines a novel role for the nuclear receptor Liver X Receptor in modulation of pulmonary innate immunity (Smoak K et al., Journal of Immunology 2008;180(5):3305-12) 2. an investigation using proteomics that has identified novel events in the response of the macrophage to lipopolysaccharide, an environmental innate immune stimulus (Dhungana S et al., Mol Cell Proteomics 2009;8:201-13) 3. a report identifying a novel association between serum cholesterol and asthma in the U.S. population, using national survey data (Fessler MB et al., J Allergy Clin Immunol 2009, in press). 4. 2 review articles on proteomic methodology (Dhungana S et al., Methods Mol Biol 2009a and 2009b) 5. a review article on the role of Toll like Receptors in metabolic syndrome (Fessler MB et al., Curr Opin Lipidol 2009) 6. a review article on mechanisms of neutrophil recruitment to the lung (Cai et al., Am J Respir Cell Mol Biol 2009, in press). In addition, one additional collaborative paper that describes a novel role for stearoyl-CoA desaturase in atherosclerosis is under revision for Arteriosclerosis, Thombosis, and Vascular Biology, and 4 additional manuscripts have recently been submitted to the journals Cell Metabolism (describes a novel role for apolipoprotein AI in innate immunity), Blood (describes effect of dyslipidemia on pulmonary host defense), Allergy (describes a new epidemiologic association between serum cholesterol and atopy in the U.S. population), and Journal of Allergy and Clinical Immunology (describes the structure of a dust mite allergen in a collaboration between our Group and the NIEHS Laboratory of Structural Biology). Additional accomplishments since our last report include receipt of a 2010 Fellow Award for Research Excellence by postdoctoral fellow Group members David Draper, Ph.D. and Jim Aloor, Ph.D., receipt of an abstract travel award as well as invitation to deliver an oral presentation to fellow David Draper at the 2009 American Thoracic Society International Conference, delivery by Group member Kathleen Smoak (biologist) of an oral presentation at the 2009 Keystone Conference on Pathogen Receptors (Banff, Canada), delivery of 5 regional research seminars by Dr. Fessler, and Chairing by Dr. Fessler of a Scientific Symposium as well as Facilitation of a poster session at the 2009 American Thoracic Society International Conference. In addition, substantial data has been collected on 5 active research projects in the laboratory: 1) characterization of apoplipoprotein A-I and apolipoprotein E as regulators of pulmonary host defense;2) characterization of the role of the cholesterol transporter ABCG1 in pulmonary host defense;and 3) proteomic identification of macrophage proteins that are modified with the fatty acid palmitate.